Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells
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Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells. / Chen, Li; Shi, Kaikai; Frary, Charles Edward; Ditzel, Nicholas; Hu, Huimin; Qiu, Weimin; Kassem, Moustapha.
I: Stem Cell Research, Bind 15, Nr. 2, 09.2015, s. 281-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells
AU - Chen, Li
AU - Shi, Kaikai
AU - Frary, Charles Edward
AU - Ditzel, Nicholas
AU - Hu, Huimin
AU - Qiu, Weimin
AU - Kassem, Moustapha
N1 - Copyright © 2015. Published by Elsevier B.V.
PY - 2015/9
Y1 - 2015/9
N2 - Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1 (LIMK1) decreased cell viability and impaired OB differentiation of hMSCs. Moreover, depolymerizing actin reduced FAK, p38 and JNK activation during OB differentiation of hMSCs, while polymerizing actin enhanced these signaling pathways. Our results demonstrate that the actin dynamic reassembly and Cofilin phosphorylation loop is involved in the control of hMSC proliferation and osteoblasts differentiation.
AB - Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1 (LIMK1) decreased cell viability and impaired OB differentiation of hMSCs. Moreover, depolymerizing actin reduced FAK, p38 and JNK activation during OB differentiation of hMSCs, while polymerizing actin enhanced these signaling pathways. Our results demonstrate that the actin dynamic reassembly and Cofilin phosphorylation loop is involved in the control of hMSC proliferation and osteoblasts differentiation.
U2 - 10.1016/j.scr.2015.06.009
DO - 10.1016/j.scr.2015.06.009
M3 - Journal article
C2 - 26209815
VL - 15
SP - 281
EP - 289
JO - Stem Cell Research
JF - Stem Cell Research
SN - 1873-5061
IS - 2
ER -
ID: 160407045